Group of a novel anti-cancer compounds with specific structure

ABSTRACT

Compounds containing a specific saturated or unsaturated branched chain terminal group; a polar leading group; and a long-chain aliphatic, non-cyclic, saturated or unsaturated, substituted or unsubstituted, hydrocarbon group linking them; and having anti-cancer, immunosuppression alleviation, immune boosting and anti-inflammation activity.

This application claims the benefit of U.S. Provisional Application60/309,487, filed Aug. 3, 2001, which application is hereby incorporatedby reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention is drawn to a group of compounds with specific structure,which possess anti-cancer activity. It also relates to their use inhuman and other mammalian subjects for cancer therapy, prevention, andimmune boosting and inflammation functions.

2. Description of the Background

JP-A 04295423 and JP-B 07072134, each to Daiichi, disclose anti-canceragents containing MeCHR(CH2)nCOOH wherein R is C1–C5 alkyl and n=4–22.U.S. Pat. No. 4,985,466 to Deguchi disclose a method for treating tumorsusceptible to treatment with a wool fatty acid, or its reduced alcohol,metal salt or aliphatic ester derivative, or a wool alcohol, or itscarboxylic acid, aliphatic ether or aliphatic ester derivative. Deguchiadditionally disclose that it is characteristic of wool fatty acid andwool alcohol to contain a large quantity of iso- and anteiso-highersaturated aliphatic acids and alcohols.

However, none of the above prior art recognizes Applicant's discoverythat the anti-cancer activity resides in a terminal branch structure anda leading end group per se directly linked at opposite ends,respectively, to a long chain group.

A group of specific iso- and anteiso-branched-chain fatty acids withsignificant anti-cancer effect has been described in Applicant's U.S.Pat. No. 6,214,875. Such compounds as described in the above Applicant'sU.S. patent, and derivatives thereof obtained by reacting the acidmoiety thereof, are described in Applicant's U.S. application Ser. No.09/647,918, which is a 371 application of PCT/US99/06525, filed Apr. 14,1999, and which was published as WO 99/53086 on Oct. 21, 1999, which WO99/53086 is hereby incorporated by reference.

These compounds have shown excellent cytotoxic activity throughinduction of apoptosis against a broad variety of cancer cells,including, but not limited to, leukemia, breast cancer, prostate cancer,lung cancer, with extremely low toxicity to experimental animals.

Applicant's WO 01/59067 describes a group of anti-cancer compounds whichare comprised of three parts: an end-terminal group, which is isopropyl,sec.-butyl, or tert.-butyl group; a leading group; and a long-chainaliphatic, non-cyclic, saturated or unsaturated, hydrocarbon group thatlinks the end-terminal group and the leading group.

This specific group of compounds, described in WO 01/59067 isillustrated by the following three formulae (1), (2) or (3):

wherein n is an integer of at least 5, m is an even integer from 0 to2b, inclusively, wherein b is the maximum number of unsaturated bonds onthe long chain (a double bond is assigned as 1 and a triple bond isassigned as 2), and R can be any polar group.

SUMMARY OF THE INVENTION

In the present invention, this specific group of compounds can befurther illustrated by the following typical structural formulae (4)through (12), and include their possible pharmaceutically acceptablesalts:

wherein n is an integer between 5 to 19, m is an integer from 0 to 2b+x,inclusively, wherein b is the maximum number of unsaturated bonds (adouble bond is assigned as 1 and a triple bond is assigned as 2), R₁,R₂, R₃ are any groups that are chemically allowed in the above formulae,provided that R₂R₃ is a polar moiety. x represents the number of groupsR₁ (x is an integer≦2n−m), which groups can be the same or different,and can be connected at the α-carbon or at any other possible position.In other words, hydrogen(s) may be replaced with R₁ in the C_(n)H_(2n−m)moiety up to the total number of available hydrogens. It is understoodthat both hydrogens on a carbon atom may be replaced with a singledivalent group, such as oxo.

However, to the extent R₁, R₂, and R₃ include groups resulting incompounds disclosed by Daiichi or Deguchi, supra, or other prior art,these compounds are excluded herein from the compounds claimed. Thus,excluded are compounds of formulae (4) and (5) wherein m=0, x=0, andR₂R₃ is —COOH or an aliphatic ester thereof or salt thereof, or R₂R₃ is—OH or an aliphatic ether thereof or aliphatic ester thereof.

DETAILED DESCRIPTION OF THE INVENTION

It should be presumed below that any differences between a chemicalstructure and its chemical name be resolved in favor of the chemicalstructure.

In the present invention, R₁ can be, but is not limited to, thefollowing:

(1) hydrogen, —H

EXAMPLES

12-Methyl-2-tetradecenoic acid,

11-Methyl-dodeca-2,4-dienoic acid,

13-Methyl-9-tetradecene acid,

12-Ethyl-12-tridecenoic acid;

(2) methyl group, —CH₃

EXAMPLE

3,11-Dimethyl-dodecanoic acid;

(3) ethyl group, —C₂H₅

EXAMPLES

9-Ethyl-11-methyl-dodecanoic acid;

(4) hydroxyl group, —OH

EXAMPLE

9-Hydroxy-11-methyl-dodecanoic acid;

(5) amino group, —NH₂

EXAMPLE

2-Amino-11-methyl-dodecanoic acid;

(6) mercapto group, —SH

EXAMPLE

9-Mercapto-11-methyl-dodecanoic acid;

(7) oxo group, ═O

EXAMPLE

9-Oxo-11-methyl-dodecanoic acid;

(8) imino group, ═NH, or hydroxyimino, ═N—OH

EXAMPLE

9-Hydroxyimino-11-methyl-dodecanoic acid;

(9) halogen

EXAMPLE

3-Chloro-11-methyl-dodecanoic acid;

(10) amino acid

EXAMPLE

9-Carboxymethylamino-11-methyl-dodecanoic acid;

(11) amino-glucose

EXAMPLE

2-Glucosamino-11-methyl-dodecanoic acid;

(12) heterocyclic ring or substituted heterocyclic

EXAMPLE

4-(8-Methyl-nonyl)-5-carboxy-tetrahydroimidazoyl-2-one,

7-(6N-Adenyl)-9-methyl-decanoic acid.

The above group or structure can be in any position of the carbon chainand the number of such group or structure is x, (x is an integer≦2n−m),which can be the same or different.

R₂ can be, but is not limited to, the following:

(1) alkoxylene group, —CH₂O

EXAMPLE

11-Methyl-9-oxo-dodecyl (3,4,5-trihydroxy)benzoate;

(2) carbonyl group,

EXAMPLE

13-Methyl-3-oxo-tetradecanal,

Sodium 15-methyl-3-oxo-1-hydroxy-hexadecylsulfonate,

N-(-13-Methyl-tetradecanoyl)-2-amino-7-ribo purine,

2N-(13-Methyl-tetradecanoyl)-guanosine,

2N-(13-Methyl-tetradecanoyl)guanine,

6N-(11-Methyl-dodecanoyl)adenine;

(3) amine group,

EXAMPLE

N,N-Diethyl-10-methylundecylamine,

N,N-di(2-aminoethyl)-12-methyl-tridecylamine tri-hydrochloride;

(4) imine group, —C═N—

EXAMPLE

13-Methyl-tetradecanal-N-hydroxyimine,

N-4-Carboxy-benzyl-(11-methyl-3-oxo-dodecyl)imine;

(5) substituted or unsubstituted phenyl group, or substituted orunsubstituted heterocyclic group

EXAMPLE

2-(10-Methyl-undecyl)-adenine hydrochloride,

2-(9-Methyl-decyl)-adenine,

2-(11-Methyldodecyl)-4-amino-pyrimidine hydrochloride.

R₃ is any possible group connecting with R₂ so that R₂R₃ is a polargroup. It can be, but is not limited to, the following:

(1) hydrogen, —H

EXAMPLE

Sodium 2-(5-hydroxy-1-imidazolyl)-11-methyl-dodecanoate;

(2) hydroxyl group, —OH

EXAMPLE

12-methyl-1,10-tridecanediol,

6-[(N-11-Methyl-dodecanoyl)glycyl]thymine;

(3) amine group,

EXAMPLE

13-Methyl-tetradecyl urea;

(4) methyl group, —CH₃, or ethyl group, —C₂H₅

EXAMPLE

(11-Methyl-9-hydroxy-dodecyl)ethyl ether;

(5) acyl group, —COR₄

EXAMPLE

12-Methyl-3-oxo-tridecyl-3,4,5-trihydroxy benzoate,

1-(2-Chloroethyl)-1-nitroso-3-(12-methyl-tridecyl)urea;

(6) sulfonyl group, —SO₂R₄

EXAMPLE

N-4-Methyl-benzenesulfonyl-13-Methyl-tetradecyl amine;

(7) hydroxyl-, halogen-, halide-, carboxyl-, carbonyl-, amino-, orglucosyl-substituted phenyl group or heterocyclic group.

EXAMPLE

(5-Carboxy-2,3,-dihydroxy phenyl)13-methyl-tetradecanoate,

6N-13-methyl-tetradecyl-5-flucytosine,

6N-(13-Methyl-tetradecanoyl)adenosine,

1N-(13-methyl-tetradecanoyl)-5-fluoropyrimidine-2,4-dione,

N,N-Di(2-chloroethyl)-4-(13-methyl-tetradecyl)aniline,

2-(2,4-Dihydroxyphenyl)-13-methyl tetradecanoic acid;

(8) hydrazine group

EXAMPLE

N-(12-methyl-tridecyl)hydrazine hydrochloride.

The R₄ and R₅ groups in the above structures can each independently be,but are not limited to, the following: hydrogen, methyl, ethyl,chloroethyl, ethoxyl, hydroxyl-,halogen-, halide-, carboxyl-, carbonyl-,amino-, or glucosyl-substituted phenyl group or heterocyclic group. R₄and R₅ can also form a heterocyclic ring such as piperidine, pyrrolidineor morpholine.

In the structure of the above compounds, the hydrogen(s) in any hydroxylgroup (—OH) or amine group (—NH₂), whether on an aliphatic chain orphenyl ring, can be replaced with a substituent to form, for example,methoxy (—OCH₃), ethyloxy (—OC₂H₅), or acetyloxy (—OCOCH₃)group.

EXAMPLES

10-Methoxy-12-methyl-tridecanol,

(12-Methyl-tridecyl)-2,4-dimethoxy benzene,

12-Methyl-3-oxo-tridecyl-3,4,5-trimethoxy-benzoate,

(5-Carboxy-2,3-dimethoxyphenyl)13-methyl-tetradecanoate.

The anti-cancer compounds described in the present invention can bechemically synthesized routinely.

Experiment 1 In vitro Anti-Cancer Efficacy

The following 49 compounds with specific structure according to thepresent invention were synthesized:

1) 12-Methyl-2-tetradecenoic acid

2) 11-Methyl-dodeca-2,4-dienoic acid

3) 13-Methyl-9-tetradecene acid

4) 12-Ethyl-12-tridecenoic acid

5) 3,11-Dimethyl-dodecanoic acid

6) 9-Ethyl-11-methyl-dodecanoic acid

7) 9-Hydroxy-11-methyl-dodecanoic acid

8) 2-Amino-11-methyl-dodecanoic acid

9) 9-Mercapto-11-methyl-dodecanoic acid

10) 9-Oxo-11-methyl-dodecanoic acid

11) 9-Hydroxyimino-11-methyl-dodecanoic acid

12) 3-Chloro-11-methyl-dodecanoic acid

13) 9-Carboxymethylamino-11-methyl-dodecanoic acid

14) 2-Glucosamino-11-methyl-dodecanoic acid

15) 4-(8-Methyl-nonyl)-5-carboxy-tetrahydroimidazoyl-2-one

16) 7-(6N-Adenyl)-9-methyl-decanoic acid

17) 11-Methyl-9-oxo-dodecyl (3,4,5-trihydroxy)benzoate

18) 13-Methyl-3-oxo-tetradecanal

19) Sodium 1-hydroxy 3-oxo-15-methyl-hexadecyl-sulfonate

20) N-(-13-Methyl-tetradecanoyl)-2-amino-7-ribo purine

21) 2N-(13-Methyl-tetradecanoyl)-guanosine

22) 2N-(13-Methyl-tetradecanoyl)guanine

23) 6N-(11-Methyl-dodecanoyl)adenine

24) N,N-Diethyl-10-methylundecylamine

25) N,N-di(2-aminoethyl)-12-methyl-tridecylamine tri-hydrochloride

26) 13-Methyl-tetradecanal-N-hydroxyimine

27) N-4-Carboxy-benzyl-(11-methyl-3-oxo-dodecyl)imine

28) 2-(10-Methyl-undecyl)-adenine hydrochloride

29) 2-(9-Methyl-decyl)-adenine

30) 2-(11-Methyldodecyl)-4-amino-pyrimidine hydrochloride

31) Sodium 2-(5-hydroxy-1-imidazolyl)-11-methyl-dodecanoate

32) 12-methyl-1,10-tridecanediol

33) 6-[(N-11-Methyl-dodecanoyl)glycyl]thymine

34) 13-Methyl-tetradecyl urea

35) (11-Methyl-9-hydroxy-dodecyl)ethyl ether

36) 12-Methyl-3-oxo-tridecyl-3,4,5-trihydroxy benzoate

37) 1-(2-Chloroethyl)-1-nitroso-3-(12-methyl-tridecyl)urea

38) N-4-Methyl-benzenesulfonyl-13-Methyl-tetradecyl amine

39) (5-Carboxy-2,3,-dihydroxy phenyl)13-methyl-tetradecanoate

40) 6N-13-methyl-tetradecyl-5-flucytosine

41) 6N-(13-Methyl-tetradecanoyl)adenosine

42) 1N-(13-methyl-tetradecanoyl)-5-fluoropyrimidine-2,4-dione

43) N,N-Di(2-chloroethyl)-4-(13-methyl-tetradecyl)aniline

44) 2-(2,4-Dihydroxyphenyl)-13-methyl tetradecanoic acid

45) N-(12-methyl-tridecyl)hydrazine hydrochloride

46) 10-Methoxy-12-methyl-tridecanol

47) (12-Methyl-tridecyl)-2,4-dimethoxy benzene

48) 12-Methyl-3-oxo-tridecyl-3,4,5-trimethoxy-benzoate

49) (5-Carboxy-2,3-dimethoxy phenyl)13-methyl-tetradecanoate

The in vitro anti-cancer efficacy tests of all the compounds above werecarried out in various human cancer cell lines including leukemia K562,NPC D562, small-cell lung cancer EKVX, colon cancer HCT116, CNS cancerSF-268, melanoma SK-MEL-5, ovarian cancer IGROV1, renal cancer RFX 393,prostate cancer DU-145, breast cancer MCF7, lung cancer H1688, livercancer SNU-423, and pancreas cancer CRL-1687. After treatment with thetest compounds and solvent control, the numbers of live cells werecounted by trypan blue dye exclusion, and IC₉₀ for various cancer celllines were calculated, ranging from 2.1 mg/ml to 49.3 mg/ml.

N-(12-methyl-tridecyl)hydrazine hydrochloride, one of the compoundsabove, was used to test the possible preventing cancer effects on mice,including breast cancer, prostate cancer, stomach cancer, lung cancerand skin cancer. More or less prevention effects were found in thetests, with rate from 30% up to 70%. The most significant effects wereobserved in preventing skin cancer.

Experiment 2 N-(12-methyl-tridecyl)hydrazine hydrochloride's Function inPreventing Ultraviolet B Ray (UVB)-Induced Skin Cancer

N-(12-methyl-tridecyl)hydrazine hydrochloride (Sample) was resolved with0.8% Tween resulting in a final concentration of 10%.

Forty female SKH-1 hairless mice were randomly divided into control andtest groups of 20 each. Each mouse in both groups was treated topicallyonce with DMBA (5.12 μg dissolved in 200 μl acetone solution) to achievetumor initiation. One week later (day 8), animals in test group startedto receive topical application of 200 μl. Sample solution once a day.The control group received 200 μl Tween 80 solvent instead every day.Thirty minutes after the application, animals in both groups wereexposed to UVB (290–320 nm) radiation at the dosage of 180 mJ/cm² perday to induce growth of tumor. The animals were evaluated for tumordevelopment at the end of 30 weeks.

The results suggest that the Sample has a preventive effect when usedduring early stage of tumor induction. At the end of the experiment, theanimals in the Sample-treated group showed a 45% reduction in tumorincidence compared to those in the control group. The average size ofcancer in the Sample-treated group was also 85% smaller.

The compounds with the specific structure disclosed in the presentinvention, including, but not limited to,N-(12-methyl-tridecyl)hydrazine hydrochloride, have a cancer preventionfunction, including for skin cancer, breast cancer, prostate cancer,stomach cancer and lung cancer.

Experiment 3 Influence of N-(12-methyl-tridecyl)hydrazine hydrochloride(Sample) on Immune Functions

1: Phagocytic Function of Reticuloendothelial System

50 female ICR strain mice, weighing 19–24 g, were randomly divided into5 groups of 10 each. One group was given N.S. at 20 ml/kg i.g. as anormal control. A positive control group was given CTX i.g. at 25 mg/kgon day 1 and 6. A third group was given N-(12-methyl-tridecyl-hydrazinehydrochloride (Sample) only at 400 mg/kg i.g. The remaining two groupswere given both CTX (25 mg/kg on day 1 and 6) and Sample (100 mg/kg and400 mg/kg, respectively). All treatments except CTX were administereddaily for 9 days. 30 minutes after the last administration, 0.15 mlYidege (1:10) was injected into the tail vein of each mouse. 1 minuteand 5 minutes after, blood was drawn and 20 μl serum was mixed with 0.1%Na₂CO₃. OD₆₈₀ was measured and the clearance index K=(1 gOD₁−1gOD₂)/(t₂−t₁) was calculated. The results were subject to t test andshown in Table 1.

TABLE 1 Effects of Sample on Serum Clearance Index of Carbon Grain inNormal and Immune-compromised Mouse P No. Compared Compared Group of Kwith with (i.g.) mice (X ± SD) Group1 Group2 N.S. 0.2 ml/10 g 10 0.0763± 0.0335 <0.001 CTX 25 mg/kg 10 0.0260 ± 0.0116 <0.001 Sample 400 mg/kg10 0.0792 ± 0.0230 >0.05 <0.001 Sample 100 mg/kg + 10 0.0433 ± 0.0401<0.001 <0.001 CTX 25 mg/kg Sample 400 mg/kg + 10 0.0603 ± 0.0371 <0.001<0.001 CTX 25 mg/kg

The results in Table 1 demonstrate that N-(12-methyl-tridecyl)hydrazinehydrochloride (Sample) had no obvious effect on the Clearance Index ofCarbon grain in normal mouse (P_(1,3)>0.05). Moreover the Sample couldeven improve the clearance of Carbon grain in CTX-treated mouse to acertain extent (both P_(2,4) and P_(2,5)<0.01).

2: Serum Hemolysinogenesis

50 male ICR strain mice, weighing 20–23 g, were randomly divided into 5groups of 10 each. The method of administration in each group was thesame as above (phagocytic function). However, on the 6th day afteradministration, 0.2 ml 3:5 (V/V) sheep red blood cell (RBC) suspensionwas injected i.p. into each mouse. 4 days later (day 10), blood wasdrawn from all animals and serum was prepared and then diluted 600times. 1 ml diluted serum was mixed with 0.5 ml 10% sheep RBCsuspension. N.S. was used as blank control. All samples were incubatedat 37° C. for 30 minutes, and centrifuged (2000 rev/min) for 5 minutes.The supernatant was collected for measurement of OD₅₄₀ and HC₅₀ wascalculated. The results were subject to t test and are shown in Table 2.

TABLE 2 Effects of Sample on Serum Hemolysinogenesis in Normal andImmune-compromised Mouse P Group No. of HC₅₀ Compared Compared (i.g.)Mice (X ± SD) with Group1 with Group2 N.S. 0.2 ml/10 g 10 34.91 ± 2.32<0.001 CTX 25 mg/kg 10 21.83 ± 4.29 <0.001 Sample 0.4 g/kg 10 32.08 ±5.06 >0.05 <0.001 Sample 0.1 g/kg + 10 22.45 ± 4.12 <0.001 >0.05 CTX 25mg/kg Sample 0.4 g/kg + 10 24.01 ± 3.87 <0.001 >0.05 CTX 25 mg/kg

The results in Table 2 show that N-(12-methyl-tridecyl)hydrazinehydrochloride (Sample) had no obvious effects on serum hemolysinogenesisin either normal or immune-compromised mouse (P_(1,3), P_(2,4), andP_(2,5)>0.05). This suggests that the Sample does not evidently affecthost humoral immunity.

3: Weights of Immune Organs

The mice were sacrificed after the Serum hemolysinogenesis test aboveand the thymus and pancreas were collected and weighed. Indices of eachorgan (mg/10 g body weight) were calculated and subject to t test, andshown in Table 3 as well.

TABLE 3 Effect of the Sample on the indices of immune organs of bothnormal and CTX-compromised mice Indices of thymus Indices of Drug Number(mg/10 g pancreas (mg/10 g (i.g.) of mice avoirdupois) avoirdupois) N.S.0.2 ml/10 g 10 3.832 ± 1.904^(a) 4.607 ± 0.883^(a) CTX 25 mg/kg 10 1.296± 0.665  2.154 ± 1.189  Sample 0.4 g/kg 10 3.617 ± 1.334^(a) 4.541 ±0.508^(a) Sample 0.1 g/kg + 10 2.448 ± 0.603^(a) 2.459 ± 0.799  CTX 25mg/kg Sample 0.4 g/kg + 10 3.307 ± 0.721^(a) 3.506 ± 1.223  CTX 25 mg/kg^(a)P < 0.001, compared to the control group.

The results in Table 3 show that there was no significant effect ofN-(12-methyl-tridecyl)hydrazine hydrochloride on the indices of immuneorgans for normal mice (both thymus and pancreases, P_(1,3)>0.05). As tothe mice that were treated by CTX, these indices increased aftercombined administration of the Sample. The increase in the indices ofthymus among these three groups is statistically significant (P_(1,2)and P_(2,4)<0.001). It is suggested that N-(12-methyl-tridecyl)hydrazinehydrochloride is different from the anticancer compounds of commonclinical use, in that it does not inhibit host immune function attherapeutic dosage.

Similarly, it was shown that the specific structured compounds disclosedin the present invention have no influence on the immune function of thenormal body and would not aggravate the immune suppression induced bychemotherapy drugs. Furthermore they have immune boosting effects andalleviate the immune suppression when used in combination with otherchemotherapy drugs.

Experiment 4 Influence of N-(12-methyl-tridecyl)hydrazine hydrochloride(Sample) on Mouse Sarcoma S₁₈₀ model

50 female ICR strain mice, weighing 19–22 g, were randomly divided into5 groups of 10 each. S₁₈₀ sarcoma mass (about 2 mm³ each) wastransplanted subcutaneously into the right armpits of all animalsfollowing standard procedure. 3 test groups were givenN-(12-methyl-tridecyl)hydrazine hydrochloride (Sample) at 0.1, 0.2, and0.4 g/kg intragastrically (i.g.) daily for 11 days. The positive controlgroup was given a single dose of cytoxan (CTX) i.g. (25 mg/kg) on day 1.The negative control group was given 0.8% Tween 80 at 0.4 ml/10 g dailyfor 11 days. On the 12th day, all mice were sacrificed and the tumor wasisolated and weighed. The rate of inhibition of tumor growth wascalculated and subject to t-test. The results are shown in Table 4.

TABLE 4 Inhibition of growth of mouse sarcoma S₁₈₀ by Sample Body WeightInhi- No. (g, X ± SD) Tumor bition of before after Weight Rate GroupMice treatment treatment (g, X ± SD) (%) 0.8% Tween 80. 10 21.8 ± 1.426.6 ± 1.8 1.10 ± 0.31  — 20 ml/kg Sample 100 mg/kg 10 21.9 ± 1.4 26.6 ±1.8 0.70 ± 0.12^(b) 36.36 Sample 200 mg/kg 10 21.9 ± 1.3 25.7 ± 1.7 0.41± 0.10^(b) 62.73 Sample 400 mg/kg 10 21.8 ± 1.3 25.0 ± 1.3 0.33 ±0.10^(b) 70.00 CTX 25 mg/kg 10 21.8 ± 1.5 25.6 ± 1.6 0.31 ± 0.11^(b)71.82 (Positive Control) ^(b)P < 0.001, compared to the control group.

Similarly, it was shown that the specific structured compounds disclosedin present invention have significant anticancer activity on human oranimal like N-(12-methyl-tridecyl)hydrazine hydrochloride does.

Experiment 5 Influence of 12-methyl-2-tetradecenoic Acid (Sample) onInflammation

12-Methyl-2-tetradecenoic acid in an oil state was directly applied onthe focus surface of oral or tongue to patients of oral adnoma andtongue cancer. It was recorded that about one week later, the focusreduced, swelling disappeared, and the patients might swallow food.

12-Methyl-2-tetradecenoic acid in an oil state was directly applied onthe inflamed surface of patients with body skin ulcerous wounds. It wasalso recorded that compared to common anti-inflammatory cream,12-Methyl-2-tetradecenoic acid has a better anti-inflammation functionand the ulcerous wound healed quickly, indicating the anti-inflammationeffects on humans.

The compounds with the specific structure in the present invention,whether chemically synthesized, or obtained through a fermentationprocess using a microorganism, or extracted from natural resources, oradministered in a natural mixture without extraction, have significantanti-cancer activity, preventing cancer, and immune boosting andanti-inflammation effects on humans and animals. These compounds canalso be taken orally or by injection, in the forms of liquid, powder,tablet, injection, capsule, or encapsulated liposome, or they can betopically applied in the forms of cream, ointment, or lotion.

1. A compound having a formula selected from the group consisting of thefollowing formulae (6) and (8) through (12):

wherein n is an integer from 5 to 19, m is an integer from 0 to 2b+x,inclusive, wherein b is the maximum number of unsaturated bonds, andwherein a double bond is assigned as 1 and a triple bond is assigned as2, and R₁, R₂, and R₃, are chemically possible groups to form thestructures above, provided that R₂R₃ is a polar moiety, x is the numberof R₁ groups (same or different) at any possible position (x is aninteger≦2n−m), and the salt thereof, and provided that when the compoundhas formula (6), m is 0, and (R₁)_(x) are all hydrogen when x is not 0,then R₂R₃ is not carboxyl.
 2. The compound of claim 1, wherein R₁ isselected from the group consisting of (1) hydrogen, (2) methyl group,(3) ethyl group, (4) hydroxyl group, (5) amino group, (6) mercaptogroup, (7) oxo group, (8) imino group, (9) halogen, (10) amino acid,(11) amino-glucose, (12) heterocyclic group and substituted heterocyclicgroup, (13) methoxy, (14) ethoxy, and (15) acetyloxy.
 3. The compound ofclaim 1, wherein R₂ is selected from the group consisting of (1)alkoxylene group, (2) carbonyl group, (3) amine group, (4) imine group,and (5) substituted or unsubstituted phenyl group, or substituted orunsubstituted heterocyclic group, including the salt thereof.
 4. Thecompound of claim 1, wherein R₃ is selected from the group consisting of(1) hydrogen, (2) hydroxyl group, (3) amine group, NR₄R₅, (4) methylgroup and ethyl group, (5) acyl group, —COR₄, (6) sulfonyl group,—SO₂R₄, (7) hydroxyl-, halogen-, halide-, carboxyl-, carbonyl-, amino-,or glucosyl-substituted phenyl group or heterocyclic group, and (8)hydrazine group, wherein the R₄ and R₅ groups are independently, thefollowing: hydrogen, methyl, ethyl, chloroethyl, ethoxyl, or hydroxyl,or hydroxyl-, halogen-, halide-, carboxyl-, carbonyl-, amino-, orglucosyl-substituted phenyl group or heterocyclic group, wherein R₄ andR₅ can also form a heterocyclic ring with N, and wherein the hydroxylgroup in (2) or (7) can be replaced with methoxy (—OCH₃), ethyloxy(—OC₂H₅), or acetyloxy (—OCOCH₃) group.
 5. A compound selected from thegroup consisting of: 11-Methyl-dodeca-2,4-dienoic acid,13-Methyl-9-tetradecene acid, 12-Ethyl-12-tridecenoic acid,9-Ethyl-11-methyl-dodecanoic acid, 9-Hydroxy-11-methyl-dodecanoic acid,2-Amino-11-methyl-dodecanoic acid, 9-Mercapto-11-methyl-dodecanoic acid,9-Oxo-11-methyl-dodecanoic acid, 9-Hydroxyimino-11-methyl-dodecanoicacid, 3-Chloro-11-methyl-dodecanoic acid,9-Carboxymethylamino-11-methyl-dodecanoic acid,2-Glucosamino-11-methyl-dodecanoic acid,4-(8-Methyl-nonyl)-5-carboxy-tetrahydroimidazoyl-2-one,7-(6N-Adenyl)-9-methyl-decanoic acid,11-Methyl-9-oxo-dodecyl(3,4,5-trihydroxy)benzoate,13-Methyl-3-oxo-tetradecanal, Sodium 1-hydroxy3-oxo-15-methyl-hexadecyl-sulfonate,N-(-13-Methyl-tetradecanoyl)-2-amino-7-ribo purine,2N-(13-Methyl-tetradecanoyl)-guanosine,2N-(13-Methyl-tetradecanoyl)guanine, 6N-(11-Methyl-dodecanoyl)adenine,N,N-Diethyl-10-methylundecylamine,N,N-di(2-aminoethyl)-12-methyl-tridecylamine tri-hydrochloride,13-Methyl-tetradecanal-N-hydroxyimine,N-4-Carboxy-benzyl-(11-methyl-3-oxo-dodecyl)imine,2-(10-Methyl-undecyl)-adenine hydrochloride, 2-(9-Methyl-decyl)-adenine,2-(11-Methyldodecyl)-4-amino-pyrimidine hydrochloride, Sodium2-(5-hydroxy-1-imidazolyl)-11-methyl-dodecanoate,12-methyl-1,10-tridecanediol, 6-[(N-11-Methyl-dodecanoyl)glycyl]thymine,13-Methyl-tetradecyl urea, (1-Methyl-9-hydroxy-dodecyl)ethyl ether,12-Methyl-3-oxo-tridecyl-3,4,5-trihydroxy benzoate,1-(2-Chloroethyl)-1-nitroso-3-(12-methyl-tridecyl)urea,N-4-Methyl-benzenesulfonyl-13-Methyl-tetradecyl amine,(5-Carboxy-2,3,-dihydroxy phenyl)13-methyl-tetradecanoate,6N-13-methyl-tetradecyl-5-flucytosine,6N-(13-Methyl-tetradecanoyl)adenosine,1N-(13-methyl-tetradecanoyl)-5-fluoropyrimidine-2,4-dione,N,N-Di(2-chloroethyl)-4-(13-methyl-tetradecyl)aniline,2-(2,4-Dihydroxyphenyl)-13-methyl tetradecanoic acid,N-(12-methyl-tridecyl)hydrazine hydrochloride,10-Methoxy-12-methyl-tridecanol, (12-Methyl-tridecyl)-2,4-dimethoxybenzene, 12-Methyl-3-oxo-tridecyl-3,4,5-trimethoxy-benzoate, and(5-Carboxy-2,3-dimethoxy phenyl)13-methyl-tetradecanoate.
 6. Thecompound of claim 5, which is N-(12-methyl-tridecyl) hydrazinehydrochloride.
 7. A method of treating inflammation comprising applyinga compound having a formula selected from the group consisting of thefollowing formulae (4) through (12):

wherein n is an integer from 5 to 19, m is an integer from 0 to 2b+x,inclusive, wherein b is the maximum number of unsaturated bonds, andwherein a double bond is assigned as 1 and a triple bond is assigned as2, and R₁, R₂, and R₃, are chemically possible groups to form thestructures above, provided that R₂R₃ is a polar moiety, x is the numberof R₁ groups (same or different) at any possible position (x is aninteger≦2n−m), and the salt thereof.
 8. The method of claim 7, whereinthe compound is 12-methyl-2-tetradecenoic acid.
 9. A compound having aformula (7):

wherein n is an integer from 5 to 19, m is an integer from 0 to 2b+x,inclusive, wherein b is the maximum number of unsaturated bonds, andwherein a double bond is assigned as 1 and a triple bond is assigned as2, and R₁, R₂, and R₃, are chemically possible groups to form thestructures above, provided that R₂R₃ is a polar moiety, x is the numberof R₁ groups (same or different) at any possible position (x is aninteger≦2n+m), and the salt thereof, provided that when R₂R₃contains aheterocyclic group, it is a nitrogen-containing heterocyclic group. 10.The compound of claim 9, wherein R₁ is selected from the groupconsisting of (1) hydrogen, (2) methyl group, (3) ethyl group, (4)hydroxyl group, (5) amino group, (6) mercapto group, (7) oxo group, (8)imino group, (9) halogen, (10) amino acid, (11) amino-glucose, (12)heterocyclic group and substituted heterocyclic group, (13) methoxy,(14) ethoxy, and (15) acetyloxy.
 11. The compound of claim 10, whereinR₂ is selected from the group consisting of (1) alkoxylene group, (2)carbonyl group, (3) amine group, (4) imine group, and (5) substituted orunsubstituted phenyl group, or substituted or unsubstitutednitrogen-containing heterocyclic group, including the salt thereof. 12.The compound of claim 10, wherein R₃ is selected from the groupconsisting of (1) hydrogen, (2) hydroxyl group, (3) amine group, NR₄R₅,(4) methyl group and ethyl group, (5) acyl group, —COR₄, (6) sulfonylgroup, —SO₂R₄, (7) hydroxyl-, halogen-, halide-, carboxyl-, carbonyl-,amino-, or glucosyl- substituted phenyl group or nitrogen-containingheterocyclic group, and (8) hydrazine group, wherein the R₄ and R₅groups are independently, the following: hydrogen, methyl, ethyl,chloroethyl, ethoxyl, or hydroxyl, or hydroxyl-, halogen-, halide-,carboxyl-, carbonyl-, amino-, or glucosyl-substituted phenyl group ornitrogen-containing heterocyclic group, wherein R₄ and R₅ can also forma heterocyclic ring with N, and wherein the hydroxyl group in (2) or (7)can be replaced with methoxy (—OCH₃), ethyloxy (—OC₂H₅), or acetyloxy(—OCOCH₃) group.